Department of Neurology, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, P. R. China.
Department of Neurology, Bengbu Second People's Hospital, Bengbu, Anhui Province, P. R. China.
Brain Behav. 2022 Dec;12(12):e2817. doi: 10.1002/brb3.2817. Epub 2022 Nov 21.
Previous studies have shown that gestational inflammation can accelerate age-associated cognitive decline (AACD) in maternal mice; enriched environments (EEs) have been reported to protect normally aging mice from AACD and improve mitochondrial function. However, it is unclear whether the nitrosative stress-related proteins tet methylcytosine dioxygenase 1 (TET1) and S-nitrosoglutathione reductase (GSNOR) are involved in the accelerated aging process of gestational inflammation and whether EEs can slow this process.
In this study, CD-1 female mice on the 15th day of pregnancy were injected with bacterial lipopolysaccharide (50 μg/kg; LPS group) or an equivalent amount of normal saline (CON group) from the abdominal cavity for 4 consecutive days. Twenty-one days after delivery, half of the LPS-treated mice were randomly selected for EE until the end of the behavioral experiment (LPS-E group). When the female rats were raised to 6 months and 18 months of age, the Morris water maze (MWM) was used to detect spatial learning and memory ability; RT-PCR and Western blots were used to measure the mRNA and protein levels of hippocampal TET1 and GSNOR.
As for the control group, compared with 6-month-old mice, the spatial learning and memory ability of 18-month-old mice decreased, and the hippocampal TET1 and GSNOR mRNA and protein levels were decreased. Gestational inflammation exacerbated these age-related changes, but an EE alleviated the effects. Pearson's correlation analysis indicated that performance during the learning and memory periods in the MWM correlated with the levels of hippocampal TET1 and GSNOR.
Our findings suggest that gestational inflammation accelerates age-related learning and memory impairments and that postpartum EE exposure could alleviate these changes. These effects may be related to hippocampal TET1 and GSNOR expression.
先前的研究表明，妊娠期炎症可加速母鼠的与年龄相关的认知衰退（AACD）；有报道称，丰富的环境（EE）可保护正常衰老的小鼠免受 AACD 的影响，并改善线粒体功能。然而，尚不清楚氧化亚氮相关蛋白 TET1 和 S-亚硝基谷胱甘肽还原酶（GSNOR）是否参与妊娠期炎症的加速衰老过程，以及 EE 是否可以减缓这一过程。
在这项研究中，妊娠第 15 天的 CD-1 雌性小鼠经腹腔注射细菌脂多糖（50μg/kg；LPS 组）或等量生理盐水（CON 组），连续 4 天。分娩后第 21 天，随机选择一半 LPS 处理的小鼠进行 EE，直至行为实验结束（LPS-E 组）。当雌性大鼠长到 6 个月和 18 个月时，使用 Morris 水迷宫（MWM）检测空间学习和记忆能力；使用 RT-PCR 和 Western blot 测定海马 TET1 和 GSNOR 的 mRNA 和蛋白水平。
与 6 月龄小鼠相比，18 月龄小鼠的空间学习和记忆能力下降，海马 TET1 和 GSNOR 的 mRNA 和蛋白水平降低。妊娠期炎症加剧了这些与年龄相关的变化，但 EE 可减轻这些变化。Pearson 相关性分析表明，MWM 学习和记忆期间的表现与海马 TET1 和 GSNOR 的水平相关。
我们的研究结果表明，妊娠期炎症加速了与年龄相关的学习和记忆障碍，产后 EE 暴露可减轻这些变化。这些影响可能与海马 TET1 和 GSNOR 的表达有关。
